Intravascular lymphomatosis presenting as skin lesions and subacute encephalopathy

Intravascular lymphomatosis is a neoplastic multisystemic disease; it is a rare subtype of diffuse large cell lymphoma characterized by the presence of lymphoma cells in the lumina of small vessels. A 49-year-old Caucasian woman was admitted to the Department of Internal Medicine for fatigue, night sweats, loss of weight, and multiple nodules in the forearms. Three months ago the patient’s family noticed problems with her cognitive function, she displayed difficulties with common daily tasks. The neurological examination revealed bradypsychia. Laboratory data showed modestly high levels of lactate dehydrogenase, and C-reactive protein. The day after admission, the patient had headache which raised in intensity; his mental status deteriorated, she was disoriented to time and place. She presented nucal rigidity. The CSF examination revealed a hemorrhagic aspect, elements 30/mm3, cytology: lymphocytes 90%, numerous erythrocytes, proteinorachia 96 mg/dL, glycorrachia 60 mg/dL. Intravenous Methylprednisolone (0.5 g two times a day) and Mannitol 20% 1g/kgw/day were administered for five days without response. She became comatose and she died six days after hospitalization. The post-mortem macroscopical brain examination showed a swallen brain, with diffuse hemorrhagic areas in the supratentorial subcortical regions. Microscopical examination showed capillaries, venules, and many arterioles distended by large malignant cells suggesting malignant lymphocytes which were intraluminal. Every organ was involved, except for bone marrow and lymph nodes. Immunohistochemical studies showed intensive staining for B cells and negative staining for factor VIII related antigen, a specific endothelial cell marker. Intravascular lymphomatosis was the post-mortem diagnostic. It represents a difficult diagnostic challenge which involves laboratory, imagistic and immunohistochemical investigations.